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A Phase I/Ib Study of NZV930 Alone and in Combination With PDR001 and /or NIR178 in Patients With Advanced Malignancies.

NCT03549000

Description:

The purpose of this study is to assess the safety, tolerability, and preliminary anti-tumor activity of experimental medication NZV930 alone and when combined with PDR001 and/or NIR178, in patients with advanced cancers

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase I/Ib Study of NZV930 Alone and in Combination With PDR001 and /or NIR178 in Patients With Advanced Malignancies.
  • Official Title: A Phase I/Ib, Open-label, Multi-center, Study of NZV930 as a Single Agent and in Combination With PDR001 and/or NIR178 in Patients With Advanced Malignancies.

Clinical Trial IDs

  • ORG STUDY ID: CNZV930X2101
  • SECONDARY ID: 2018-000153-51
  • NCT ID: NCT03549000

Conditions

  • Non-small Cell Lung Cancer (NSCLC)
  • Triple Negative Breast Cancer (TNBC)
  • Pancreatic Ductal Adenocarcinoma (PDAC)
  • Colorectal Cancer Microsatellite Stable (MSS)
  • Ovarian Cancer
  • Renal Cell Carcinoma (RCC)

Interventions

DrugSynonymsArms
NIR178NZV930 with NIR178 Doublet Therapy

Purpose

The purpose of this study is to assess the safety, tolerability, and preliminary anti-tumor activity of experimental medication NZV930 alone and when combined with PDR001 and/or NIR178, in patients with advanced cancers

Trial Arms

NameTypeDescriptionInterventions
NZV930 MonotherapyExperimentalSingle Agent NZV930
    NZV930 with PDR001 Doublet TherapyExperimentalCombination of NZV930 with PDR001
      NZV930 with NIR178 Doublet TherapyExperimentalCombination of NZV930 with NIR178
      • NIR178
      NZV930 with NIR178 & PDR001 Triplet TherapyExperimentalCombination of NZV930 with NIR178 and PDR001
      • NIR178

      Eligibility Criteria

              Inclusion Criteria:
      
              Adult men & women ≥ 18 years of age Histologically confirmed advanced malignancies with
              documented progression following standard therapy, or for whom, in the opinion of the
              investigator, no appropriate standard therapy exists.
      
              Must have a site of disease amenable to biopsy and be a candidate for tumor biopsy
              according to the treating institution's guidelines. The patient must be willing to undergo
              a new tumor biopsy at screening and during treatment.
      
              ECOG performance status 0-2 and in the opinion of the investigator, likely to complete at
              least 56 days of treatment.
      
              Exclusion Criteria:
      
              Symptomatic or uncontrolled Brain metastases requiring concurrent treatment, inclusive of
              but not limited to surgery, radiation and/or corticosteroids.
      
              Patients with treated symptomatic brain metastases should be neurologically stable for 4
              weeks post-treatment prior to study entry and at doses of ≤10 mg per day prednisolone or
              equivalent for at least 2 weeks before administration of any study treatment.
      
              Patients who required discontinuation of treatment due to treatment-related toxicities with
              prior immunotherapy.
      
              Patients previously treated with anti-CD73 treatment and/or adenosine receptor A2a (A2aR)
              inhibitors.
      
              Active, previously documented, or suspected autoimmune disease within the past 2 years.
      
              Patients with vitiligo, type I diabetes, residual hypothyroidism only requiring hormone
              replacement, psoriasis not requiring systemic treatment or conditions not expected to recur
              should not be excluded. Additionally, patients previously exposed to anti-PD-1/PD-L1
              treatment who are adequately treated for skin rash or with replacement therapy for
              endocrinopathies should not be excluded.
      
              History of or current drug-induced interstitial lung disease or pneumonitis grade ≥ 2.
      
              Impaired cardiovascular function or clinically significant cardiovascular disease,
              including any of the following: Clinically significant and/or uncontrolled heart disease
              such as congestive heart failure requiring treatment (NYHA Grade ≥ 2), uncontrolled
              hypertension or clinically significant arrhythmia Patients with corrected QT using the
              Fridericia's correction (QTcF) > 470 msec for females or >450 msec for males, on screening
              ECG or congenital long QT syndrome Acute myocardial infarction or unstable angina < 3
              months prior to study entry History of stroke or transient ischemic event requiring medical
              therapy Symptomatic claudication Infection: HIV infection, Active HBV or HCV infection (per
              institutional guidelines). Patients with chronic HBV or HCV disease that is controlled
              under antiviral therapy are allowed in the expansion but not in the escalation, Known
              history of tuberculosis Infection requiring systemic antibiotic therapy. Patients requiring
              systemic antibiotics for infection must have completed treatment before screening is
              initiated.
      
              Systemic anti-cancer therapy within 2 weeks of the first dose of study treatment. For
              cytotoxic agents that have major delayed toxicity, e.g. mitomycin C and nitrosoureas, 6
              weeks is indicated as washout period. For patients receiving anticancer immunotherapies, 4
              weeks is indicated as the washout period.
      
              Systemic chronic steroid therapy (≥ 10 mg/day prednisone or equivalent) or any
              immunosuppressive therapy, other than replacement dose steroids in the setting of adrenal
              insufficiency, within 7 days of the first dose of study treatment. Topical, inhaled, nasal,
              and ophthalmic steroids are allowed
      
              Other protocol-defined inclusion/exclusion criteria may apply
            
      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Number of participants with adverse events as a measure of safety and tolerability of the NZV930 in combination with PDR001 and/or NIR178
      Time Frame:3 years
      Safety Issue:
      Description:Incidence and severity of AEs and SAEs, incl. changes in laboratory parameters, vital signs, and ECGs Dose limiting toxicity in cycle 1 (28 days) for single agent NZV930 and NZV930 in combination with PDR001 and/or NIR178 during dose escalation phase only Tolerability: dose interruptions Tolerability: dose reductions Tolerability: dose intensity

      Secondary Outcome Measures

      Measure:Overall response rate (ORR)
      Time Frame:3 years
      Safety Issue:
      Description:Defined as the proportion of patients with best overall response of CR or PR
      Measure:Clinical Benefit Rate (CBR)
      Time Frame:3 years
      Safety Issue:
      Description:Defined as the proportion of patients with best overall response of CR, PR or SD >= 16 weeks
      Measure:Progression Free Survival (PFS)
      Time Frame:3 years
      Safety Issue:
      Description:Defined as the time from the date of start of treatment to the date of the event defined as first documented progression or death due to any cause
      Measure:Serum concentration vs. time profiles of NZV930 (free drug) and PDR001.
      Time Frame:3 years
      Safety Issue:
      Description:Serum concentration vs. time profiles of NZV930 (free drug) and PDR001.
      Measure:Plasma concentration vs. time profiles for NIR178 and derived PK parameters
      Time Frame:3 years
      Safety Issue:
      Description:Concentration time profile of NIR178 and its metabolites
      Measure:To assess the immunogenicity of NZV930 and PDR001
      Time Frame:3 years
      Safety Issue:
      Description:Presence and titer of anti-drug antibodies, anti-NZV930 and anti-PDR001 in (patients receiving combination with PDR001).
      Measure:Characterize changes in the immune infiltrate in tumors
      Time Frame:3 years
      Safety Issue:
      Description:Change from baseline in tumor infiltrating lymphocytes (TILs), tumor associated macrophages (TAMs), CD8+ T-cells, and PDL-1 expression

      Details

      Phase:Phase 1
      Primary Purpose:Interventional
      Overall Status:Recruiting
      Lead Sponsor:Novartis Pharmaceuticals

      Trial Keywords

      • NZV930
      • PDR001
      • NIR178
      • Immune checkpoint inhibitor
      • immunotherapy
      • CD73
      • PD-1
      • PD-L1
      • A2aR
      • Adenosine

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